The incidence of hepatocellular carcinoma (HCC) is rising in the U.S and is projected to become the 3rd leading cause of cancer death by 2030. Over 90% of HCC occur in cirrhosis, and HCC is the leading cause of death for these patients. Although several professional societies recommend use of abdominal ultrasound and alpha fetoprotein (AFP), a serum biomarker, every 6 months in patients with cirrhosis, limitations in the literature have precluded consensus recommendations. Two systematic reviews concluded prior studies have notable limitations including a lack of data regarding screening harms. Potential harms of HCC screening include: 1) physical and financial harms from diagnostic evaluation in screen-positive patients (e.g., contrast injury, radiation exposure, biopsy complications); 2) overdiagnosis; and 3) psychosocial harms due to positive or indeterminate screen results. Because the survival benefit of HCC screening appears modest, a comprehensive harms assessment is needed to inform guidelines, build consensus among primary care providers and specialists, and guide patient and provider decision-making about HCC screening. Leveraging a multi-center randomized trial assessing screening benefits in a socioeconomically (~30% underinsured) and racially diverse (>50% Black or Hispanic) population of 3000 patients with cirrhosis followed in 3 healthcare settings (academic tertiary care center, safety-net health system, and Veterans Affairs system) over a 4-year period, we propose to: Aim 1: Assess the effect of HCC screening on a) physical harms due to follow-up tests, b) financial harms, and c) overdiagnosis in patients with severe liver dysfunction or comorbid illness, through electronic medical record data, manual chart review, and validated survey measures Aim 2: Assess the effect of HCC screening on screening-related psychosocial harms, e.g. cancer-specific worry, situational anxiety, mood disturbances, and decisional regret, through longitudinal validated measures and qualitative interviews Aim 3: Create and disseminate a balance sheet of benefits and harms to inform patients, nurses, providers, healthcare organizations, payers, and policymakers about the value of HCC screening in patients with cirrhosis We will use mixed-effect regression analysis to identify if screening-related harms differ by patient, provider, and healthcare system factors. These data will complement concurrently collected data about screening benefits from the randomized trial to provide the highest quality data available about benefits and harms of HCC screening at a time when policy decisions about HCC screening are being made. We will immediately translate our study findings to facilitate patient-provider discussions, inform payer decisions about reimbursement, and guide policy decisions on HCC screening in patients with cirrhosis.